CD4+ T Cells Recognizing a Single Self-Peptide Expressed by APCs Induce Spontaneous Autoimmune Arthritis
| Autor: | Soyoung Oh, Brigitte Koeberlein, Cristina Cozzo Picca, Malinda Aitken, Ali Naji, Laura Panarey, Amy J. Reed, Andrew L. Rankin, Peter E. Lipsky, Joseph Larkin, Andrew J. Caton, Heath M. Guay, John E. Tomaszewski |
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| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Genetically modified mouse Inflammatory arthritis Transgene Immunology Antigen presentation Antigen-Presenting Cells Arthritis Mice Transgenic Autoantigens T-Lymphocytes Regulatory Autoimmune Diseases Proinflammatory cytokine Mice Immune system Animals Immunology and Allergy Medicine Promoter Regions Genetic Antigen Presentation B-Lymphocytes MHC class II biology business.industry Histocompatibility Antigens Class I medicine.disease Hemagglutinins biology.protein Peptides business |
| Zdroj: | The Journal of Immunology. 180:833-841 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.180.2.833 |
| Popis: | We have examined processes leading to the spontaneous development of autoimmune inflammatory arthritis in transgenic mice containing CD4+ T cells targeted to a nominal Ag (hemagglutinin (HA)) and coexpressing HA driven by a MHC class II promoter. Despite being subjected to multiple tolerance mechanisms, autoreactive CD4+ T cells accumulate in the periphery of these mice and promote systemic proinflammatory cytokine production. The majority of mice spontaneously develop inflammatory arthritis, which is accompanied by an enhanced regional immune response in lymph nodes draining major joints. Arthritis development is accompanied by systemic B cell activation; however, neither B cells nor Ab is required for arthritis development, since disease develops in a B cell-deficient background. Moreover, arthritis also develops in a recombinase activating gene-deficient background, indicating that the disease process is driven by CD4+ T cells recognizing the neo-self HA Ag. These findings show that autoreactive CD4+ T cells recognizing a single self-Ag, expressed by systemically distributed APCs, can induce arthritis via a mechanism that is independent of their ability to provide help for autoantibody production. |
| Databáze: | OpenAIRE |
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